Nanotechnology is having an increasing impact in the healthcare industry, offering unprecedented capability of not only carrying multiple diagnostic/therapeutic payloads in the same composition, but also facilitating the targeted delivery into specific sites and across complex biological barriers.
RNA interference (RNAi) mediated silencing or downregulation of mRNA is an established technique for inhibiting gene expression. However, a major hurdle limiting the use of the gene silencing technology is the lack of methods to safely and efficiently deliver siRNA molecules to target cells/tissues. In free form, siRNA molecules have a very short half life in physiological conditions, owing to their vulnerability for degradation by endogeneous nucleases. In addition, their permeability across cellular membranes is extremely limited. Furthermore, free siRNA is completely inaccessible to the brain, which is a major target organ for the delivery of various siRNA-based therapeutics. The brain is secluded from the systemic circulation owing to the presence of the blood brain barrier (BBB), which excludes the brain specific delivery of 100% of large-molecule neurotherapeutics and more than 98% of all small-molecule drugs (Pardridge W M (2007). Advanced Drug Delivery Reviews 59(2-3):141-152). Therefore, there is a need ongoing need for improved compositions and methods for siRNA delivery, which will not only protect the siRNA from physiological degradation, but also help them permeate across biological barriers such as cellular membranes and the BBB.